AGING IN SUBMANDIBULAR CELLS MAKING GROWTH FACTORS

小鼠下颌下腺是已知的最丰富的表皮细胞来源， 生长因子（EGF）和神经生长因子（NGF），它们在体内合成， 这个腺体只由导管的一个专门部分的细胞组成，称为 颗粒曲小管（GCT）。 GCT细胞分泌这些因子 是由α肾上腺素能激动剂刺激的 雄激素和甲状腺激素 导致GCT细胞肥大，并诱导高水平的 EGF和EGF。 我们最近报告了一个明显的结构性下降， C57 B1/6高龄雄性小鼠的GCT区室，伴随80%的GCT区室异常。 EGF在皮肤中的浓度降低。 我们设计了一个 体视学模型，以确定每个腺体的GCT细胞总数，如 以及平均单核GCT（MGCT）细胞的体积。 当这些 数据与任一生长的总腺体含量相关 通过放射免疫测定的GF因子，每个MGCT细胞的GF量 可以被建立。 通过比较MGCT的这些定量参数， 从成熟（12个月）和老年（28个月以上）雄性小鼠的细胞，我们将测试 假设在GCT细胞中观察到的结构和成分下降 与衰老有关的疾病是由于内在的功能障碍。 我们将 比较成熟和老化的MGCT细胞对急性炎症反应的能力， 通过研究α肾上腺素能激动剂苯肾上腺素的刺激， EGF和NGF的分泌和恢复的程度和速率，表达 每个MGCT细胞。 我们还将比较他们的荷尔蒙反应，在这些 二氢睾酮慢性刺激的两个年龄， 通过研究三碘甲状腺原氨酸的诱导程度和速率， MGCT细胞肥大，以及每个MGCT细胞两个GF的增加。 这些研究将有助于了解生理作用， 在成熟和老年个体中，这两种生物学上有效的 多肽，其对生长具有显著和广泛的影响， 和各种组织的分化。 这些信息可以证明 有助于解释随着年龄的增长，生长控制的变化。

The mouse submandibular gland is the richest known source of epidermal growth factor (EGF) and nerve growth factor (NGF), which are synthesized in this gland only by cells of a specialized portion of the duct, known as the granular convoluted tubule (GCT). Secretion of these factors by GCT cells is stimulated by alpha adrenergic agonists. Androgens and thyroid hormones cause hypertrophy of GCT cells, and induce the synthesis of high levels of NGF and EGF. We have recently reported a marked structural decline in the GCT compartment of C57Bl/6 male mice of advanced age, accompanied by an 80% reduction in EGF concentration in the gland. We have designed a stereologic model to determine the total number of GCT cells per gland, as well as the volume of the average mononuclear GCT (MGCT) cell. When these data are correlated with the total glandular content of either growth factor (GF) determined by radioimmunoassay, the amount of GF per MGCT cell can be established. By comparing these quantitative parameters of MGCT cells from mature (12 mo) and aged (28+ mo) male mice, we will test the hypothesis that the structural and compositional declines seen in GCT cells with senescence are due to intrinsic functional impairments. We will compare the ability of mature and aged MGCT cells to respond to acute stimulation by the alpha andrenergic agonist, phenylephrine, by studying the extent and rate of secretion and restitution of EGF and NGF, expressed per MGCT cell. We will also compare their hormonal responsiveness at these two ages to chronic stimulation by dihydrotestosterone and triiodothyronine, by studying the extent and rate of induction of hypertrophy of MGCT cells, and of increases of the two GFs per MGCT cell. These studies will contribute to an understanding of the physiologic role, in mature and aged individuals, of these two biologically potent polypeptides, which have pronounced and wide-spread effects on the growth and differentiation of a variety of tissues. Such information may prove helpful in explaining changes in control of growth with advancing age.